Abstract:
BACKGROUND:Mechanical ventilation can cause ventilator-induced lung injury (VILI) and lung fibrosis; however, the underlying mechanisms are still not fully understood. RNA sequencing is a powerful means for detecting vitally important protein-coding transcripts and long non-coding RNAs (lncRNAs) on a genome-wide scale, which may be helpful for reducing this knowledge gap. METHODS:Ninety C57BL/6 mice were subjected to either high tidal volume ventilation or sham operation, and then mice with ventilation were randomly allocated to periods of recovery for 0, 1, 3, 5, 7, 14, 21, or 28 days. Lung histopathology, wet-to-dry weight ratio, hydroxyproline concentration, and transforming growth factor beta 1 (TGF-β1) levels were determined to evaluate the progression of inflammation and fibrosis. To compare sham-operated lungs, and 0- and 7-day post-ventilated lungs, RNA sequencing was used to elucidate the expression patterns, biological processes, and functional pathways involved in inflammation and fibrosis. RESULTS:A well-defined fibrotic response was most pronounced on day 7 post-ventilation. Pairwise comparisons among the sham and VILI groups showed a total of 1297 differentially expressed transcripts (DETs). Gene Ontology analysis determined that the stimulus response and immune response were the most important factors involved in inflammation and fibrosis, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed that mechanistic target of rapamycin (mTOR), Janus kinase-signal transducer and activator of transcription (JAK/STAT), and cyclic adenosine monophosphate (cAMP) signaling were implicated in early inflammation; whereas TGF-β, hypoxia inducible factor-1 (HIF-1), Toll-like receptor (TLR), and kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were significantly involved in subsequent fibrosis. Additionally, 332 DE lncRNAs were identified and enriched in the processes of cellular and biological regulation. These lncRNAs may potentially regulate fibrosis through signaling pathways such as wingless/integrase-1 (Wnt), HIF-1, and TLR. CONCLUSIONS:This is the first transcriptome study to reveal all of the transcript expression patterns and critical pathways involved in the VILI fibrotic process based on the early inflammatory state, and to show the important DE lncRNAs regulated in inflammation and fibrosis. Together, the results of this study provide novel perspectives into the potential molecular mechanisms underlying VILI and subsequent fibrosis.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Wang L,Zhang N,Zhang Y,Xia J,Zhan Q,Wang Cdoi
10.1186/s12931-018-0822-zsubject
Has Abstractpub_date
2018-06-22 00:00:00pages
122issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-018-0822-zjournal_volume
19pub_type
杂志文章abstract:BACKGROUND:Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. M...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-14-55
更新日期:2013-05-20 00:00:00
abstract:BACKGROUND:An increasing number of epidemiological and experimental studies have associated exposure to second-hand smoke (SHS) during pregnancy with adverse outcomes in newborns. As we have previously shown in mice, in utero exposure to SHS at critical stages of fetal development, results in altered lung responses and...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0591-0
更新日期:2017-06-27 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-43
更新日期:2011-04-10 00:00:00
abstract:BACKGROUND:Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate i...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0886-9
更新日期:2018-09-20 00:00:00
abstract::The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 μg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 μg) and standard-dose (4 puffs, 400 μg) salbut...
journal_title:Respiratory research
pub_type: 信件,随机对照试验
doi:10.1186/s12931-017-0632-8
更新日期:2017-08-03 00:00:00
abstract::There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1108-9
更新日期:2019-07-08 00:00:00
abstract:BACKGROUND:Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0380-1
更新日期:2016-05-26 00:00:00
abstract:INTRODUCTION:Bacteria have been extensively implicated in the development of smoking related diseases, such as COPD, by either direct infection or bacteria-mediated inflammation. In response to the health risks associated with tobacco exposure, the use of electronic cigarettes (e-cigs) has increased. This study compare...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1206-8
更新日期:2019-12-18 00:00:00
abstract:RATIONALE:Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged. METHODS:Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, pea...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0229-z
更新日期:2015-06-13 00:00:00
abstract:RESEARCH QUESTION:There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. PATIENTS A...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01600-z
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:While glucocorticoids are currently the most effective therapy for asthma, associated side effects limit enthusiasm for their use. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activators include the synthetic thiazolidinediones (TZDs) which exhibit anti-inflammatory effects that suggest usef...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-90
更新日期:2007-12-04 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is associated with inflammatory response but it is unknown whether it is associated with alterations in NNMT activity and MNA plasma concentration. Here we examined changes in NNMT-MNA pathway in PAH in rats and humans. METHODS:PAH in rats was induced by a single subcut...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0423-7
更新日期:2016-08-31 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiati...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-10-80
更新日期:2009-08-29 00:00:00
abstract:BACKGROUND:Several small molecule corrector and potentiator drugs have recently been licensed for Cystic Fibrosis (CF) therapy. However, other aspects of the disease, especially inflammation, are less effectively treated by these drugs. We hypothesized that small molecule drugs could function either alone or as an adju...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1214-8
更新日期:2019-12-21 00:00:00
abstract::Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted i...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-20
更新日期:2014-02-17 00:00:00
abstract:BACKGROUND:Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile ...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0950-5
更新日期:2018-12-07 00:00:00
abstract:BACKGROUND:Impaired skeletal muscle regeneration could contribute to the progression of muscle atrophy in patients with chronic obstructive pulmonary disease (COPD). METHODS:Satellite cells and myogenesis-related proteins were compared between healthy subjects and patients with COPD, with or without muscle atrophy. Sa...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-35
更新日期:2014-03-25 00:00:00
abstract:BACKGROUND:The investigation of mesenchymal stromal cell (MSC)-conditioned medium or extracellular vesicles (exosomes or microvesicles) as a remedy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has become a fast-growing field in recent years. Our purpose was to conduct a meta-analysis to inv...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01574-y
更新日期:2020-11-20 00:00:00
abstract:BACKGROUND:Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma. METHODS:In the Isle of Wight birth cohort ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-2
更新日期:2008-01-10 00:00:00
abstract:BACKGROUND:Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of tr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0153-7
更新日期:2014-11-29 00:00:00
abstract:BACKGROUND:Several studies have investigated the prevalence and risk factors of insomnia in subjects with obstructive sleep apnea syndrome. However, few studies have investigated the prevalence and risk factors for obstructive sleep apnea syndrome in insomnia sufferers. Thus, the aim of this study was to examine the pr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0616-8
更新日期:2017-07-06 00:00:00
abstract:BACKGROUND:Human beta-defensin-4 (hBD-4), a new member of the beta-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrob...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-130
更新日期:2005-11-04 00:00:00
abstract::Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokin...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr17
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD:Statistical patterns of subjective and objective findings were assessed by retrospective chart re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-149
更新日期:2005-12-19 00:00:00
abstract:BACKGROUND:CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-25
更新日期:2005-03-05 00:00:00
abstract:BACKGROUND:Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown tha...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章
doi:10.1186/1465-9921-6-81
更新日期:2005-07-24 00:00:00
abstract:BACKGROUND:Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene have recently been identified in recessively inherited veno-occlusive disease. In this study we assessed if EIF2AK4 mutations occur also in a family with autosomal dominantly inherited pulmonary arterial hypertension (HPAH) ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0457-x
更新日期:2016-11-04 00:00:00
abstract:BACKGROUND:Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1101-3
更新日期:2019-06-24 00:00:00
abstract:BACKGROUND:Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0452-2
更新日期:2016-10-27 00:00:00
abstract:BACKGROUND:ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0735-x
更新日期:2018-02-13 00:00:00